Heliobacter Pylori
Heliobacter Pylori (H. pylori), is a gram-negative bacterium found primarily in the stomach, and is found in higher numbers in patients with chronic gastritis or peptic ulcers, as well as duodenal ulcers and stomach cancer. Over 50% of the general population have it present in the upper GI tract, and 80% of those are asymptomatic, suggesting it may play a role in natural stomach ecology. Microbiology 'Characteristics' H. pylori is a helix-shaped bacterium that requires oxygen to function, (but it must be at lower concentrations than that of the atmosphere). It obtains energy in the stomach by using a hydrogenase to oxidise the hydrogen (H2) released by other intestinal bacteria. They are capable of forming a biofilm over parts of the stomach lining, which may facilitate its survival in the harsh acidic environment. The outer membrane consists of phospholipids and lipopolysaccharide (LPS), whose O antigen may mimic that of the blood antigens on the gastric epithelium if fucosylated. LPS tends to elicit strong immune responses from the body. The bacteria possess 5 main protein families on the outer side of their membranes: *Adhesins allow for the attachment of the bacteria to other bacteria and other surfaces *Porins are large molecule channels that allow for specific, passive diffusion of molecules which are ordinarily not able to do so *Iron transport proteins facilitate the movement of iron into the cell *Flagellum associated proteins have various functions relating to the function of the 4-6 lophitrichous flagella (i.e. to facilitate chemotaxis) *An family of unknown function 'Detection' There are several methods of eliciting whether a bacterium or culture is H. pylori, including a gram stain, Giemsa stain, haematoxylin-eosin stain, Warthin-Starry stain, acridine-orange stain, or a phase-contrast microscopy. 'Genetics' There is a vast array of different strains, and roughly 29% of the loci in the studied genomes are responsible for pathogenicity. There is a 'pathogenicity island' containing over 40 genes that is absent in those who have the bacteria present but are asymptomatic, suggesting these are the genes responsible for disease. The cagA gene codes for one of the major virulence proteins, and H. pylori containing this gene are more strongly associated with the ability to cause ulcers. Part of the cagA gene codes for the complex type IV secretion system which allows for the 'injection' of molecules into host cells. Pathophysiology 'Adaptation to acidic stomach environment' Heliobacter pylori avoids the harsh acidic environment of the stomach by using its 4-6 flagella to burrow itself into the mucus lining of the stomach until it reaches the epithelial cells underneath, where pH is more favourable. It knows which way to travel as it can sense the pH gradient of the mucus. This burrowing and subsequent adhesion also prevents it from being swept away into the lumen. H. pylori can be found in the mucus, adhered to the epithelial cells, or even within the cells themseles. Adhesins on its surface bind to lipids and carbohydrates expressed on the epithelial cell membranes; for example BabA binds to the the Lewis b antigen displayed on stomach epithelial cells. H. pylori further negates the effects of the highly acidic environment through the production and release of large amounts of urease, an enzyme which breaks down urea in the stomach into (CO2 and) ammonia, a strong base that neutralises the stomach acid. 'Inflammation, gastritis, and ulceration' There are a few mechanisms via which H. pylori can damage the stomach and duodeal linings. The ammonia (and CO2) produced by the action of its urease enzyme is toxic to epithelial cells, as are other substances it releases, including vaculoating cytotoxin A (VacA), which causes apoptosis, and cytotoxin associated gene (CagA) which stimulates inflammation and has links to carcinogenicity. Cysteine rich proteins (particularly HcpA) are also known to trigger a strong immune response facilitating the inflammation. A buildup of H. Pylori can lead to chronic gastritis at the site of infection. Ulcers in the stomach and duodenum result when inflammation becomes servere enough that stomach acid and pepsin overwhelm the protective mechanisms and mucosal linings at a site. A hotspot of infection is the pylorus (entrance to duodenum), where the bacteria can colonise easily due to its distance from the acid-secreting cells of the fundus (near entrance to stomach). The body's responds to colonisation in the pylorus by stimulating the release of gastrin from G cells in the vicinity. Gastrin travels in the bloodstream to act on the parietal cells of the fundus. It binds to cholecystokinin B receptors to stimulate histamine release, and moreover, the insertion of K+/H+ pumps into the apical membranes of parietal cells, thereby increasing the release of H+, meaning more stomach acid. H. pylori 'injects' its effector molecules into epithelial cells using a type IV secretion system (a system for release and uptake of macromolecules). Peptidoglycan is an integral part of bacterial membranes and an inflammation-inducing agent that the bacterian can inject. It binds to Nod1 receptors in the cell, stimulating inflammatory cytokine release. The same secretion mechanism also injects CagA, which causes the majority of negative effects; mucosal breakdown, cytoskeleton disruption, cellular signalling failures, etc. Signs and symptoms The vast majority of those infected with H. pylori (85%) are completely asymptomatic and never experience any complications. Those that do present with acute gastritis, abdominal pain, or nausea. Chronic gastritis is more often functional (non-ulcer) dyspepsia and may present with bloating, belching, vomiting, or black stools. Those with H. pylori infections have 10-20% chance of developing peptic ulcers at some point in their lifetime, and a 1-2% chance of getting stomach cancer. Colonisations of the pylorus are more likely to lead to ulcers, whereas colonisation of the body of the stomach is more likely to result in gastric carcinomas and may be indicative of other problems (as colonisation of the body is usually only possible in those that do not produce sufficient stomach acid. Diagnosis The colonisation of the stomach is not a disease in itself but is the cause of many upper GI tract conditions. If there is suspicion of peptic ulcers, low grade MALT lymphomas, gastric cancer, 1st degree relatives with gastric cancer, or dyspepsia, then testing is recommended. Several routes of testing exist; blood antibody tests, stool antigen tests, or most commonly, the carbon urea breath test, where patients drink C13/C14 radioactively labelled urea, which the bacteria metabolises into ammonia and CO2. The CO2 can be detected in the breath. The most reliable method however, is a biopsy check during an endoscopy. There is also a urine ELISA test with high sensitivity and almost 80% specificity. Prevention and treatment There is some progress in the creation of a vaccine against the bacteria in response to rising antibiotic resistance. However, research does suggest that the effect that its presence has on wider systemic immune responses is a factor in the reduction of prevalence of asthma, rhinitis, dermatitis, and others, so a vaccine is unlikely to become widely available soon. The standard approach to follow after the discovery of a peptic ulcer is a one week triple therapy of a proton pump inhibitor (e.g. omeprazole), and the antiobiotics clarityromycin and amoxicillin. Any of the components of the triple therapy may be substituted in certain cases (e.g. those with a penicillin allergy), although antibiotic resistance is a growing problem.